title: Depression of axonal excitability by valproate is antagonized by phenytoin.
abstract: Standard electrophysiologic techniques were employed to determine the effects of the two anticonvulsants, valproic acid (VPA) and phenytoin (DPH), on the membrane excitability properties of the crayfish giant axon. VPA, 4 mM, produces a depolarization of the membrane that is associated with a decrease in the resting membrane conductance (gM). VPA also attenuates the increase in gNa and gK that are responsible for the depolarization and repolarization of the action potential; it decreases the magnitude, rate of depolarization and repolarization, and conduction velocity of the propagated action potential while increasing its duration. DPH has some effects on membrane properties that are qualitatively similar to those of VPA; 0.11 mM DPH also decreases gM, gNa, and gK. Unlike VPA, DPH does not have a significant effect on magnitude of either the resting or action potential. Pretreatment of axons with DPH reduces the effect of VPA on the magnitude, rate of depolarization and repolarization, and duration of the action potential while completely preventing the effects of VPA on resting potential, conduction velocity, and membrane conductance. These experiments and others on the effects of K(+) depolarization on membrane properties demonstrate that part, but not all, of the influence of VPA on the membrane is secondary to its depolarizing effect. The results reported here on a membrane model suggest at least part of the cellular basis for the anticonvulsant properties of VPA and DPH, alone and in combination.
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D003400:Astacoidea; D001369:Axons / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D009431:Neural Conduction / Q000187:drug effects; D010672:Phenytoin / Q000494:pharmacology*; D014635:Valproic Acid / Q000037:antagonists & inhibitors*
chemical_list: D014635:Valproic Acid; D010672:Phenytoin